MicroRNA-7 Deficiency Ameliorates the Pathologies of Acute Lung Injury through Elevating KLF4.
MicroRNA-7 Deficiency Ameliorates the Pathologies of Acute Lung Injury through Elevating KLF4.
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MicroRNA-7 缺陷通过升高 KLF4 改善急性肺损伤的病理学
DOI：
10.3389/fimmu.2016.00389
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发表时间：
2016
影响因子：
7.3
通讯作者：
Xu L
中科院分区：
文献类型：
--
作者：
Zhao J;Chen C;Guo M;Tao Y;Cui P;Zhou Y;Qin N;Zheng J;Zhang J;Xu L
最近的证据表明microRNA-7（miR-7）在肺相关疾病的病理学中起重要作用。然而，miR-7在急性肺损伤（ALI）中的潜在作用仍然知之甚少。在此，我们评估了miR-7缺陷对ALI病理学的影响。我们首先发现LPS诱导的小鼠ALI模型肺组织中miR-7的表达上调。值得注意的是，我们通过使用miRNA-Sponge技术产生了miR-7敲低小鼠，并发现miR-7缺陷可以改善肺的病理学，如在ALI小鼠中加速的体重恢复、降低的支气管肺泡灌洗（BAL）促炎细胞因子水平和减少的BAL细胞数量。此外，BAL中各种免疫细胞的比例和数量，包括天然免疫细胞F4/80+巨噬细胞、γδT细胞、NK 1.1 + T细胞和CD 11 c + DC，以及适应性免疫细胞CD 4 + T细胞和CD 8 + T细胞也分别发生了显著变化。机制证据显示，在ALI模型中，miR-7的靶分子KLF 4在肺组织中表达上调，并伴随NF-κB、AKT和ERK通路的改变。这些数据提供了以前未知的miR-7在ALI病理学中的作用，这可能最终有助于理解ALI的发展和针对临床炎症性肺病的新治疗策略的开发。
Recent evidence showed that microRNA-7 (miR-7) played an important role in the pathologies of lung-related diseases. However, the potential role of miR-7 in acute lung injury (ALI) still remains poorly understood. Here, we assessed the effect of miR-7 deficiency on the pathology of ALI. We, first, found that the expression of miR-7 was upregulated in lung tissue in murine LPS-induced ALI model. Notably, we generated miR-7 knock down mice by using miRNA-Sponge technique and found that miR-7 deficiency could ameliorate the pathologies of lung as evidenced by accelerated body weight recovery, reduced level of bronchoalveolar lavage (BAL) proinflammatory cytokines and decreased number of BAL cells in ALI mice. Moreover, the proportion and number of various immune cells in BAL, including innate immune cell F4/80+ macrophages, γδT cells, NK1.1+ T cells, and CD11c+DCs, as well as adaptive immune cell CD4+ T cells and CD8+ T cells, also significantly changed, respectively. Mechanistic evidence showed that KLF4, a target molecule of miR-7, was upregulated in lung tissues in ALI model, accompanied by altered transduction of NF-κB, AKT, and ERK pathway. These data provided a previously unknown role of miR-7 in pathology of ALI, which could ultimately aid the understanding of development of ALI and the development of new therapeutic strategies against clinical inflammatory lung diseases.
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影响因子：
30.5
作者：
通讯作者：
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影响因子：
5.4
作者：
George, Jeffy;Lewis, Mark G.;Mattapallil, Joseph J.
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影响因子：
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作者：
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通讯作者：
Xu, Lin
影响因子：
168.9
作者：
Brusselle, Guy G.;Joos, Guy F.;Bracke, Ken R.
通讯作者：
Bracke, Ken R.
影响因子：
4.8
作者：
Gorbatenko, Andrej;Olesen, Christina W.;Pedersen, Stine F.
通讯作者：
Pedersen, Stine F.